The major goal of this project remains the understanding of the pathophysiology of age changes in the human cerebrum. Our several approaches are based on our past studies of the ultrastructure of the senile plaque and the neurofibrillary tangle which implicate synaptic pathology and neurofibrous protein. During the coming year we will continue to study the morphologic changes in the brains of aged animals of various species. The recovery stages of dying back neuropathy are to be investigated since the changes are analogous to those found in the plaque. The effects of ischemia and hypoxia on axon terminals will be looked at. The relation between amyloid deposition and neurite degeneration will be studied in animals with spontaneous and induced amyloidosis.